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Diabetes 53:1890-1893, 2004
© 2004 by the American Diabetes Association, Inc.

Brief Genetics Report

A 212-kb Region on Chromosome 6q25 Containing the TAB2 Gene Is Associated With Susceptibility to Type 1 Diabetes

David Owerbach, Lazaro Piña, and Kenneth H. Gabbay

From the Molecular Diabetes and Metabolism Section and the Harry B. and Aileen B. Gordon Diabetes Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas

The IDDM5 gene, which is identified by whole-genome searches, is located on chromosome 6q25. TAB2 (MAP3K7IP2 [mitogen-activating protein kinase kinase kinase 7 interacting protein 2]) is a potential candidate gene for type 1 diabetes because it is located on chromosome 6q25 and is involved in nuclear factor (NF)-{kappa}B regulation. We have conducted familial association studies using 478 families and demonstrate that a type 1 diabetes susceptibility gene resides within a 212-kb region containing the TAB2 gene (Tsp = 1.0 x 10–2 to 4.0 x 10–4). No amino acid polymorphisms were detected in TAB2; however, multiple single nucleotide polymorphisms (SNPs) found within 5' untranslated, 3' untranslated, and intron regions were associated with type 1 diabetes susceptibility. Two additional genes, LOC340152, a predicted gene with currently unknown function, and SMT3, which has homology to SUMO (small ubiquitin-related modifier) were found within the 212-kb region and were associated with type 1 diabetes susceptibility. Functional studies of the three genes will be required to determine their biological relevance to type 1 diabetes. However, both TAB2 and SUMO are involved in NF-{kappa}B activation and may thus be involved in type 1 diabetes through apoptosis in pancreatic ß-cells.

Address correspondence and reprint requests to Dr. David Owerbach, Department of Pediatrics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030. E-mail: davido{at}bcm.tmc.edu

Abbreviations: LD, linkage disequilibrium; NF, nuclear factor; SBE, single base extension; SNP, single nucleotide polymorphism; SUMO, small ubiquitin-related modifier; TAB2, mitogen-activating protein kinase kinase kinase 7 interacting protein 2; TDT, transmission disequilibrium test


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Copyright © 2004 by the American Diabetes Association.